The investigators are requesting the continuation of a training grant in support of a predoctoral program promoting excellence in the toxicological sciences, focusing on molecular mechanisms of environmental chemical induced toxicity and disease. The Program is located at two geographically close sites within the University of Texas (UT) system, and which have multiple, well established training and research collaborations. These interactions are fostered by a joint NIEHS sponsored Center for Research on Environmental Disease (CRED) and a shared T35 training grant that supports summer research training for undergraduate minority students on both campuses. An important aspect of this program is the graduation of trainees who are actively recruited by colleagues from around the nation. This training program is particularly effective at attracting underrepresented groups into the discipline of Toxicology (women and minorities). Although each trainee selects from a wide variety of ongoing research programs, and works primarily in the laboratory of one of the training faculty, the training program promotes and supports collaborative research. The research programs of the training faculty include: 1) mechanisms of experimental and human carcinogenesis (Conti); 2) mechanisms and regulation of protein kinases (Dalby); 3) molecular mechanisms of multi-stage skin carcinogenesis (DiGiovanni); 4) role of inflammation in chemical carcinogenesis (Fischer); 5) hormonal carcinogenesis (Fuchs-Young); 6) E2F transcription factors (Johnson); 7) free radical biochemistry and molecular mechanisms of apoptosis (Kehrer); 8) role of vitamin E in signaling pathways leading to cell death (Kline and Sanders); 9) metabolism, chemical-induced nephro-carcinogenicity, prostaglandin mediated cytoprotection and proteomics (Lau); 10) molecular interactions of carcinogens with chromatin (MacLeod); 11) molecular mechanisms of oncotic and apoptotic cell death in response to reactive oxygen species (ROS)-induced DNA damage, ROS-induced changes in chromatin structure and function (Monks); 12) male reproductive toxicology and germ cellapoptosis (Richburg); 13) mechanisms of apoptosis in epithelial tumorigenesis (Tang); 14) mechanisms of DNA damage recognition by DNA repair and recombination pathways (Vasquez); and, 15) role of genetic alterations in tumor development (Walker). Predoctoral trainees are evaluated for admission into the training program on the basis of GPA, GRE, letters of recommendation previous research experience, and interviews. Progress is monitored throughout the year by participation, each semester, in seminars, course work, research progress in the laboratory, and an annual report prepared by the trainees describing their progress. Faculty have an excellent history of collaboration and sharing of research resources, such as advanced instrumentation, that foster multidisciplinary research. Thus, (i) the maturity of the graduate program, (ii) the clear demand for the graduates which exceeds the investigators' supply, (iii) the institutional commitment to the educational mission of the toxicology program via the establishment of the Center for Molecular and Cellular Toxicology, (iv) in combination with the established NIEHS Center (CRED), all combine to provide an environment ideal for an increase in the number of NIEHS supported predoctoral positions. The investigators therefore believe this is the optimum time to expand the training grant.